Mouse models of cancer in which primary tumors are driven by specifically engineered oncogenes have been increasingly useful tools in cancer research in recent years. Although they require relatively long timeframes for genetic crosses and latency of spontaneous tumors, current methods of producing such genetically engineered mice generally have been adequate for producing relatively small numbers of genotypes for basic research.
Primary tumors from mouse models would be particularly useful in drug development studies, as well as in basic research. This is because similar or indistinguishable tumor phenotypes, e.g., breast carcinoma, can undergo neoplastic transformation through the spontaneous acquisition of different mutations, which leads to different tumor cell genotypes. Due to the different genotypes of different tumors, a given drug may be efficacious against one tumor but not against the another tumor of the same phenotype. Consequently, conventional xenograft experiments using an established human cancer cell line are likely to provide an incomplete picture. For the same reason, clinical trial data simply will indicate that the drug is effective in some patients but not others.
In spite of the desirability of genetically defined primary tumor material for drug development studies, the time and resources that would be required to generate the necessary mouse models have made it impractical to design preclinical drug development studies around the use of primary tumor material in which tumorigenicity depends on a pre-selected gene of interest, i.e., target gene.